<jats:title>Abstract</jats:title><jats:p>Growth of<jats:italic>Streptomyces</jats:italic>in submerged culture is characterized by the formation of complex mycelial particles, known as pellets or clumps, which strongly influence antibiotic production. Also, many bioactive molecules produced by<jats:italic>Streptomyces</jats:italic>have great potential to modulate soil bacteria morphological development. However, there has been no effort directed at engineering mycelial morphology using these small molecules. Here, thiostrepton was identified, using a combination of qRT-PCR, semi-preparative HPLC, and MALDI-TOF MS, as a pellet-inducing compound produced by<jats:italic>S. laurentii</jats:italic>ATCC31255. At sub-inhibitory concentration, thiostrepton stimulated<jats:italic>Streptomyces coelicolor</jats:italic>M145 pellet formation and antibiotics production were altered, with 3-fold and 2-fold decreases in actinorhodin and undecylprodigiosin yields, respectively. It was also shown that mycelial morphology can be influenced by other antibiotic class at sub-inhibitory concentrations. For instance, in the presence of spectinomycin,<jats:italic>S. coelicolor</jats:italic>M145, which under typical growth conditions forms large diameter pellets with many protruding hyphae, instead formed small diameter pellets with barely visible hyphae at the edge. Importantly, this morphology produced a 4-fold increase in undecylprodigiosin production and 3-fold decrease in actinorhodin production. These results indicated that these small molecules, previously identified as antimicrobials, also have great potential for influencing mycelial morphology.